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Phosphoglycerate kinase 1 as a therapeutic target in neurological disease. 磷酸甘油酸激酶1作为神经系统疾病的治疗靶点。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-04-14 DOI: 10.1016/j.molmed.2025.03.008
Harriet McHale-Owen, Kiterie M E Faller, Helena Chaytow, Thomas H Gillingwater
{"title":"Phosphoglycerate kinase 1 as a therapeutic target in neurological disease.","authors":"Harriet McHale-Owen, Kiterie M E Faller, Helena Chaytow, Thomas H Gillingwater","doi":"10.1016/j.molmed.2025.03.008","DOIUrl":"https://doi.org/10.1016/j.molmed.2025.03.008","url":null,"abstract":"<p><p>Phosphoglycerate kinase 1 (PGK1) is a highly conserved enzyme that catalyzes the initial ATP-producing step in glycolysis. Improving cellular energy production by increasing PGK1 activity may be beneficial in multiple neurological conditions where cell metabolism is dysregulated, including Parkinson's disease (PD) and motor neuron disease (MND). This review examines recent evidence that suggests increasing PGK1 activity may be beneficial in multiple neurological conditions and discusses the current challenges surrounding the development of PGK1-focused therapies. PGK1 has considerable therapeutic potential, but novel PGK1 activators are needed to maximize the benefit for patients.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
MicroRNAs in the biology and hallmarks of neurodegenerative diseases. 神经退行性疾病的生物学和标志中的microrna。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-04-07 DOI: 10.1016/j.molmed.2025.03.006
Shivnarayan Dhuppar, Wolfram C Poller, Gopal Murugaiyan
{"title":"MicroRNAs in the biology and hallmarks of neurodegenerative diseases.","authors":"Shivnarayan Dhuppar, Wolfram C Poller, Gopal Murugaiyan","doi":"10.1016/j.molmed.2025.03.006","DOIUrl":"https://doi.org/10.1016/j.molmed.2025.03.006","url":null,"abstract":"<p><p>A combination of intracellular and extracellular abnormalities of the nervous system, coupled with inflammation and intestinal dysbiosis, form the hallmarks of neurodegenerative diseases (NDDs). While it is difficult to identify the precise order in which these hallmarks manifest in NDDs because of their mutualistic nature, they cumulatively result in nervous or neuronal damage that characterizes neurodegeneration. In this review we discuss the roles of microRNAs (miRNAs) in the maintenance of nervous system homeostasis and their implication for NDDs. We further highlight recent advances in, and limitations of, miRNA therapeutics in NDDs and their future potential.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pushing the boundaries: future directions in the management of spinal muscular atrophy. 突破界限：脊髓性肌萎缩症治疗的未来方向。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-04-01 Epub Date: 2025-01-09 DOI: 10.1016/j.molmed.2024.12.006
Fiona Moultrie, Laura Chiverton, Isabel Hatami, Charlotte Lilien, Laurent Servais
{"title":"Pushing the boundaries: future directions in the management of spinal muscular atrophy.","authors":"Fiona Moultrie, Laura Chiverton, Isabel Hatami, Charlotte Lilien, Laurent Servais","doi":"10.1016/j.molmed.2024.12.006","DOIUrl":"10.1016/j.molmed.2024.12.006","url":null,"abstract":"<p><p>Spinal muscular atrophy (SMA) is a devastating, degenerative, paediatric neuromuscular disease which until recently was untreatable. Discovery of the responsible gene 30 years ago heralded a new age of pioneering therapeutic developments. Three disease-modifying therapies (DMTs) have received regulatory approval and have transformed the disease, reducing disability and prolonging patient survival. These therapies - with distinct mechanisms, routes of administration, dosing schedules, side effect profiles, and financial costs - have dramatically altered the clinical phenotypes of this condition and have presented fresh challenges for patient care. In this review article we discuss potential strategies to maximise clinical outcomes through early diagnosis and treatment, optimised dosing, use of therapeutic combinations and state-of-the-art physiotherapy techniques, and the development of innovative therapies targeting alternative mechanisms.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"307-318"},"PeriodicalIF":12.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genetic causes of obesity: mapping a path forward. 肥胖的遗传原因：绘制前进的路径。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-04-01 Epub Date: 2025-03-14 DOI: 10.1016/j.molmed.2025.02.002
Ruth J F Loos
{"title":"Genetic causes of obesity: mapping a path forward.","authors":"Ruth J F Loos","doi":"10.1016/j.molmed.2025.02.002","DOIUrl":"10.1016/j.molmed.2025.02.002","url":null,"abstract":"<p><p>Over the past 30 years, significant progress has been made in understanding the genetic causes of obesity. In the coming years, catalogs that map each genetic variant to its genomic function are expected to accelerate variant-to-function (V2F) translation. Given that obesity is a heterogeneous disease, research will have to move beyond body mass index (BMI). Gene discovery efforts for more refined adiposity traits are poised to reveal additional genetic loci, pointing to new biological mechanisms. Obesity genetics research is reaching unprecedented heights and, along with a renewed interest in the development of weight-loss medication, it holds the potential to identify new drug targets. Polygenic scores (PGSs) that predict obesity risk are expected to further improve and will be particularly valuable early in life for timely prevention.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"319-325"},"PeriodicalIF":12.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cystic fibrosis at a glance: from disease mechanism to therapy. 囊性纤维化概览：从发病机制到治疗。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-04-01 Epub Date: 2025-03-21 DOI: 10.1016/j.molmed.2025.02.001
Kasper Gryspeert, Laudonia L Dipalo, Ana L Da Silva Cunha, Mattijs Bulcaen, Marjolein M Ensinck, Marianne S Carlon
{"title":"Cystic fibrosis at a glance: from disease mechanism to therapy.","authors":"Kasper Gryspeert, Laudonia L Dipalo, Ana L Da Silva Cunha, Mattijs Bulcaen, Marjolein M Ensinck, Marianne S Carlon","doi":"10.1016/j.molmed.2025.02.001","DOIUrl":"10.1016/j.molmed.2025.02.001","url":null,"abstract":"","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"399-400"},"PeriodicalIF":12.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Here's to 30 Years of Trends in Molecular Medicine! 为分子医学30年的发展趋势干杯！
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-04-01 DOI: 10.1016/j.molmed.2024.12.011
Aliki Perdikari
{"title":"Here's to 30 Years of Trends in Molecular Medicine!","authors":"Aliki Perdikari","doi":"10.1016/j.molmed.2024.12.011","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.12.011","url":null,"abstract":"","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":"31 4","pages":"297"},"PeriodicalIF":12.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Engineering cytokines for tumor-targeting and selective T cell activation. 用于肿瘤靶向和选择性T细胞活化的工程细胞因子。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-04-01 Epub Date: 2025-02-14 DOI: 10.1016/j.molmed.2025.01.010
Kun Peng, Yang-Xin Fu, Yong Liang
{"title":"Engineering cytokines for tumor-targeting and selective T cell activation.","authors":"Kun Peng, Yang-Xin Fu, Yong Liang","doi":"10.1016/j.molmed.2025.01.010","DOIUrl":"10.1016/j.molmed.2025.01.010","url":null,"abstract":"<p><p>Cytokines are promising therapeutic agents for cancer due to their immune-stimulating properties. However, their clinical application is limited by a narrow therapeutic window and dose-limiting on-target, off-tumor toxicity. Advances in protein engineering enable the selective delivery of cytokines to the tumor microenvironment (TME) and antigen-specific T cells, enhancing antitumor efficacy while reducing systemic side effects. This review focuses on selected cytokines and outlines their developmental trajectory for treating solid tumors. We highlight strategies for constructing cis-signaling immunocytokines and procytokines for precise delivery to tumor sites and discuss the biological mechanisms through which these cytokines reactivate antitumor immunity. We also discuss the challenges and future directions for creating more effective cytokine-based therapeutics.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"373-387"},"PeriodicalIF":12.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The bleeding edge: broadening horizons for hematopoietic stem cell therapies. 前沿：拓宽造血干细胞治疗的视野。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-04-01 Epub Date: 2025-03-21 DOI: 10.1016/j.molmed.2025.03.003
Spencer D Shelton, Vijay G Sankaran
{"title":"The bleeding edge: broadening horizons for hematopoietic stem cell therapies.","authors":"Spencer D Shelton, Vijay G Sankaran","doi":"10.1016/j.molmed.2025.03.003","DOIUrl":"10.1016/j.molmed.2025.03.003","url":null,"abstract":"<p><p>Recent reports of gene therapy using autologous hematopoietic stem cell transplantation (HSCT) have addressed protein deficiencies of extra-hematopoietic origin. In a recent study, Srivastava et al. report that patients with hemophilia A receiving F8 lentiviral HSCT gene therapy achieved lasting factor VIII restoration and clinical improvement, marking an advance that could enable broader applications of HSCT.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"301-303"},"PeriodicalIF":12.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Adeno-associated viral vector targeted evolution for neurofibromatosis gene delivery. 腺相关病毒载体靶向进化用于神经纤维瘤病基因传递。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-04-01 Epub Date: 2025-01-30 DOI: 10.1016/j.molmed.2025.01.004
Brett Henshey, Ana Carneiro, Kecheng Lei, David Schaffer, Nicholas M Boulis
{"title":"Adeno-associated viral vector targeted evolution for neurofibromatosis gene delivery.","authors":"Brett Henshey, Ana Carneiro, Kecheng Lei, David Schaffer, Nicholas M Boulis","doi":"10.1016/j.molmed.2025.01.004","DOIUrl":"10.1016/j.molmed.2025.01.004","url":null,"abstract":"<p><p>Neurofibromatosis type 1 (NF1) is an inherited genetic disease resulting from pathogenic mutations in NF1 that drive tumor formation along peripheral nerves, leading to many functional consequences. Tumor removal or treatment often results in regrowth and/or nerve damage. Addressing NF1 pathogenic variations at the cellular level through gene therapy holds great potential for long-term treatment of patients with NF1. Adeno-associated viruses (AAVs) are broadly used gene delivery vehicles for gene therapies because of their low pathogenicity, ability to transduce nondividing cells, and potential for long-term gene expression. This article explores the landscape of AAV-mediated gene delivery strategies for NF1, discusses the challenges of efficient delivery to relevant cell types, and highlights the progress in vector design strategies.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"388-398"},"PeriodicalIF":12.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A sex-biased target against demyelination in Alzheimer's disease. 针对阿尔茨海默病脱髓鞘的性别偏见靶点。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-04-01 Epub Date: 2025-03-24 DOI: 10.1016/j.molmed.2025.03.004
Kelsey R Babcock, Doudou Yu, Ashley E Webb
{"title":"A sex-biased target against demyelination in Alzheimer's disease.","authors":"Kelsey R Babcock, Doudou Yu, Ashley E Webb","doi":"10.1016/j.molmed.2025.03.004","DOIUrl":"10.1016/j.molmed.2025.03.004","url":null,"abstract":"<p><p>Aging and Alzheimer's disease (AD) exhibit sex differences in several biological processes, including demyelination. In a recent study, Lopez-Lee et al. uncover the contributions of sex chromosomes and gonadal hormones to sex differences in demyelination and identify Toll-like receptor 7 (TLR7) as a potential target to ameliorate tauopathy-induced demyelination in men.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"304-306"},"PeriodicalIF":12.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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